The generation of surfaces and interfaces that are able to withstand protein adsorption is a major challenge in the design of blood-contacting materials for both medical implants and bioaffinity sensors. Poly(ethylene glycol)-derived materials are generally considered to be particularly effective candidates for the fabrication of protein-resistant materials. Most metallic biomaterials are covered by a protective, stable oxide film; converting such oxide surfaces, which are known to strongly interact with proteins, into noninteractive surfaces requires a specific design of the surface/interface architecture. A class of copolymers based on poly(L-lysine)g-poly(ethylene glycol) (PLL-g-PEG) was found to spontaneously adsorb from aqueous solutions onto several metal oxide surfaces, such as TiO 2 , Si 0.4 Ti 0.6 O 2 , and Nb 2 O 5 , as measured by the in situ optical waveguide lightmode spectroscopy technique and by ex situ X-ray photoelectron spectroscopy. The resulting adsorbed layers are highly effective in reducing the adsorption both of blood serum and of individual proteins such as fibrinogen, which is known to play a major role in the cascade of events that lead to biomaterial-surfaceinduced blood coagulation and thrombosis. Adsorbed protein levels as low as <5 ng/cm 2 could be achieved for an optimized polymer architecture. The modified surfaces are stable to desorption under flow conditions at 37 °C and pH 7.4 in HEPES [4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid] and PBS (phosphatebuffered saline) buffers. The adsorbed layer of copolymer is thought to form a comblike structure at the surface, with positively charged primary amine groups of the PLL bound to the negatively charged metal oxide surface, while the hydrophilic and uncharged PEG side chains are exposed to the solution phase.Copolymer architecture is an important factor in the resulting protein resistance; it is discussed on the basis of packing-density considerations and the corresponding radii of gyration of the different PEG chain lengths studied. This surface functionalization technology is believed to be of value for use in both the biomaterial and biosensor areas, as the chosen macromolecules are biocompatible and the application is straightforward and cost-effective. † Part of the special issue "Gabor Somorjai Festschrift".

Poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG) is a member of a family of polycationic PEG-grafted copolymers that have been shown to chemisorb on anionic surfaces, including various metal oxide surfaces, providing a high degree of resistance to protein adsorption. PLL-g-PEG-modified surfaces are attractive for a variety of applications including sensor chips for bioaffinity assays and blood-contacting biomedical devices. The analytical and structural properties of PLL-g-PEG adlayers on niobium oxide (Nb2O5), tantalum oxide (Ta2O5), and titanium oxide (TiO2) surfaces were investigated using reflection-absorption infrared spectroscopy (RAIRS), angle-dependent X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). The combined analytical information provides clear evidence for an architecture with the cationic poly(L-lysine) attached electrostatically to the oxide surfaces (charged negatively at physiological pH) and the poly(ethylene oxide) side chains extending out from the surface. The relative intensities of the vibrational modes in the RAIRS spectra and the angle-dependent XPS data point to the PLL backbone being located directly at and parallel to the oxide/polymer interface, whereas the PEG chains are preferentially oriented in the direction perpendicular to the surface. Both positive and negative ToF-SIMS spectra are dominated by PEG-related secondary ion fragments with strongly reduced metal (oxide) intensities pointing to an (almost) complete coverage by the densely packed PEG comblike grafts. The three different transition metal oxide surfaces with isoelectric points well below 7 were found to behave very similarly, both in respect to the kinetics of the polymer adlayer adsorption and properties as well as in terms of protein resistance of the PLL-g-PEG-modified surface. Adsorption of serum and fibrinogen was evaluated using the OWLS optical planar waveguide technique. The amount of human serum adsorbed on the modified surfaces was consistently below the detection limit of the optical sensor technique used (<1-2 ng cm -2 ), and fibrinogen adsorption was reduced by 96-98% in comparison to the nonmodified (bare) oxide surfaces.